Comparative immunoinformatic analysis of Rhipicephalus microplus cocktail vaccine targets

Authors: HENDAWY, SEHAM - Washington State University; ALZAN, HEBA - Washington State University; Ueti, Massaro

Submitted to: Parasites & Vectors
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/7/2025
Publication Date: 12/9/2025
Citation: Hendawy, S.H., Alzan, H.F., Ueti, M.W. 2025. Comparative immunoinformatic analysis of Rhipicephalus microplus cocktail vaccine targets. Parasites & Vectors. 18(1). Article 502. https://doi.org/10.1186/s13071-025-07109-y.
DOI: https://doi.org/10.1186/s13071-025-07109-y

Interpretive Summary: Rhipicephalus microplus is common in tropical and subtropical regions. Infestations cause significant economic losses for beef and dairy producers by transmitting disease-causing pathogens. Tick proteins found in the gut, salivary glands, and ovaries are essential for water regulation, reproduction, and cell membrane integrity. We conducted comprehensive bioinformatic and immunoinformatic analyses to assess these proteins as potential vaccine targets for R. microplus control. By examining physicochemical properties, protein topology, glycosylation and phosphorylation sites, B-cell and T-cell epitopes, and immune response simulations, we identified key epitopes and characterized their behavior in the host. These results support the development of a multicomponent vaccine to effectively control Rhipicephalus ticks.

Technical Abstract: Background: The cattle fever tick, Rhipicephalus microplus (R. microplus), is found in tropical and subtropical regions worldwide. These infestations lead to significant economic losses for cattle producers and dairy farmers, and they can transmit a variety of pathogens that cause diseases such as babesiosis, anaplasmosis, and theileriosis. Bm86, AQP1, AQP2, and VgR proteins are expressed in various tick tissues, including the gut, salivary glands, and ovaries. These proteins regulate essential physiological processes such as water balance (AQP1, AQP2), reproduction (VgR), and cell membrane integrity (Bm86). Methods: Comprehensive bioinformatic and immunoinformatic analyses were conducted to evaluate Bm86, AQP1, AQP2, and VgR as potential vaccine targets against R. microplus. The physicochemical properties, topographical protein analysis, prediction of N-glycosylation sites, O-glycosylation sites, phosphorylation sites, B-cell and T-cell epitopes, and immune response simulation of these proteins helped identify key epitopes, highlighting their behavior within the host, representing a promising multicomponent vaccine formulation. Results: The predictions for R. microplus Bm86, VgR, AQP1, and AQP2 proteins indicate strong antigenicity, low allergenicity, and minimal toxicity, suggesting the potential for safe and effective immune response elicitation. Furthermore, immune profile simulations for a cocktail of these proteins as vaccine candidates predict consistently high levels of IFN-gamma and antibody isotypes, which could improve vaccine efficacy and control tick fitness and survivability in subsequent generations.